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Biomedical subjects

Alan J Magill

Publications and source records attributed to Alan J Magill.

18 recordsLinked to original sources
PubMed2006

Fever in patients with mixed-species malaria.

BACKGROUND: Clinical symptoms of mixed-species malaria infections have been variously reported as both less severe and more severe than those of single-species infections. METHODS: Oral temperatures were taken from and blood slides were prepared for 2308 adults who presented at outpatient malaria clinics in Tak Province (Thailand) during May-August 1998, May-July 1999, and May-June 2001 with malaria infections diagnosed by 2 expert research microscopists, each of whom was blinded to the other's reports. RESULTS: In each year, temperatures of patients with mixed Plasmodium vivax-Plasmodium falciparum infections were higher than temperatures of patients with P. vivax or P. falciparum infections. In every mixed-species case, P. falciparum parasitemia was higher than P. vivax parasitemia, but patient temperature was not correlated with the parasitemia of either species or with the total parasitemia. CONCLUSIONS: Among adults who self-report to malaria clinics in western Thailand, patients with mixed P. vivax-P. falciparum infections have higher fevers than patients with single-species infections, a distinction that cannot be attributed to differences in parasitemia. This observation warrants more detailed investigations, spanning wider ranges of ages and transmission environments.

Adult↗
PubMed2006

Malaria: diagnosis and treatment of falciparum malaria in travelers during and after travel.

Plasmodium falciparum is responsible for most of the mortality in travelers related to imported malaria. Problems that occur during travel include the inaccuracy of a microscopic diagnosis of malaria, both false positives and false negatives, when ill travelers seek care while abroad. A false positive diagnosis can result in unnecessary parenteral injections that carry a risk of transmission of blood-borne pathogens, receipt of potentially dangerous drugs such as halofantrine, or receipt of fake, counterfeit drugs. Increased morbidity and mortality are associated with delays in diagnosis and initiation of prompt treatment for falciparum malaria. Availability of expert microscopy to confirm the diagnosis of malaria is limited. The presence of splenomegaly and thrombocytopenia are strongly associated with malaria and would justify empiric treatment. The availability of atovaquone-proguanil, a safe and well tolerated oral drug, should prompt a reconsideration of current treatment recommendations that discourage empiric treatment on clinical suspicion alone.

Journal Article↗
PubMed2006

Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I.

Primaquine phosphate has been used for preventing relapse of Plasmodium vivax and P. ovale malaria since the early 1950s, based on its ability to kill latent (hypnozoite) and developing liver stages of these parasites. There are three uses for primaquine in malaria: radical cure of established infection with P. vivax or P. ovale malaria; presumptive anti-relapse therapy (PART; terminal prophylaxis) in persons with extensive exposure to these parasites; and primary prophylaxis against all malaria species. All persons for whom primaquine is being considered must have a glucose-6-phosphate dehydrogenase (G6PD) enzyme level checked before use, and persons who have a deficiency of G6PD must not take primaquine for prophylaxis or PART. The recommended adult dose for PART based on clinical trials and expert opinion is 30 mg base daily for 14 days, started on return from a malarious region and overlapping with a blood schizonticide. The adult dose for primary prophylaxis is 30 mg daily begun 1 day before travel and continued for 7 days after return. This review will examine the evidence for these recommendations.

Adult↗
PubMed2006

Epidemiology and spatial analysis of malaria in the Northern Peruvian Amazon.

A retrospective surveillance study was conducted to examine the micro-geographic variation of malaria incidence in three malaria-endemic communities in the Northern Peruvian Amazon. The annual malaria risk rate (per 100) ranged from 38% to 47% for Plasmodium vivax and from 15% to 18% for P. falciparum. Spatial clusters were found for P. vivax in Padre Cocha, Manacamiri, and Zungaro Cocha, and for P. falciparum only in Padre Cocha. Spatial-temporal clusters showed that the highest monthly number of P. vivax cases varied every year from December to March in 1996-1997 and from February to June in 1998-1999, and for P. falciparum from November to April in 1996-1997 and from January to April in 1998-1999. Our results suggest a constant presence of high-risk areas (hot spots) for malaria infection in periods with high or low malaria incidence. Modest targeted control efforts directed at identified high-risk areas may have significant impact on malaria transmission in this region.

Cluster Analysis↗
PubMed2005

White blood cell counts and malaria.

White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999. At each site and in each year, WBC counts in the Plasmodium falciparum-infected patients were lower than those in the Plasmodium vivax-infected patients, which, in turn, were lower than those in the uninfected patients. In Thailand, one-sixth of the P. falciparum-infected patients had WBC counts of <4000 cells/microL. Leukopenia may confound population studies that estimate parasite densities on the basis of an assumed WBC count of 8000 cells/microL. For instance, in the present study, use of this conventional approach would have overestimated average asexual parasite densities in the P. falciparum-infected patients in Thailand by nearly one-third.

Adolescent↗
PubMed2005

Cutaneous leishmaniasis in the returning traveler.

Infection with protozoan parasites of the genus Leishmania leads to a wide variety of clinical disease syndromes called leishmaniasis, or more appropriately the leishmaniases. The three major clinical syndromes are cutaneous leishmaniasis, mucosal leishmaniasis, and visceral leishmaniasis. All three of these syndromes have been documented in returning travelers. This article focuses on cutaneous leishmaniasis with some comment on mucosal leishmaniasis.

Animals↗
PubMed2005

Randomized, double-blind, phase III, pivotal field trial of the comparative immunogenicity, safety, and tolerability of two yellow fever 17D vaccines (Arilvax and YF-VAX) in healthy infants and children in Peru.

We conducted a randomized, double-blind, phase III yellow fever (YF) vaccine trial among 1,107 healthy children in Sullana in northern Peru. The safety and efficacy (by measurement of geometric mean neutralizing antibody titer responses) were determined for two YF vaccines, ARILVAX (n = 738) and YF-VAX(R) (n = 369). Serocon-version rates were higher (94.9%) in ARILVAX than in YF-VAX (90.6%) recipients. The two-sided 95% confidence interval (YF-VAX-ARILVAX) was (-12.8% to -2.5%), indicating that the higher seroconversion rate for Arilvax was significant. Post-vaccination (30-day) mean log(10) neutralization indices were found to be similar for both products: 1.32 for ARILVAX and 1.26 for YF-VAX (P = 0.1404, by analysis of variance). A similar number of subjects in each group reported at least one adverse event (AE); 441 (59.8%) for ARILVAX versus 211 (59.9%) for YF-VAX. Most (591; 96.7%) of these were of a mild nature and resolved without treatment. There were no treatment-related serious AEs. This is the first randomized, double-blind comparison of two YF vaccines in a pediatric population; both vaccines were shown to be highly immunogenic and well-tolerated.

Antibodies, Viral↗
PubMed2005

Sources of variability in determining malaria parasite density by microscopy.

Enumeration of parasites by microscopic examination of blood smears is the only method available for quantifying parasitemia in infected blood. However, the sources and scale of error inherent in this technique have not been systematically investigated. Here we use data collected in outpatient clinics in Peru and Thailand to elucidate important sources of variation in parasite density measurements. We show that discrepancies between readings from two independent microscopists and multiple readings from a single microscopist are inversely related to the density of the infection. We present an example of how differences in reader technique, specifically the number of white blood cells counted, can contribute to the differences between readings. We discuss the implications of this analysis for field studies and clinical trials.

Animals↗
PubMed2004

Nontraumatic deaths during U.S. Armed Forces basic training, 1977-2001.

BACKGROUND: A Recruit Mortality Registry, linked to the Department of Defense Medical Mortality Registry, was created to provide comprehensive medical surveillance data for deaths occurring during enlisted basic military training. METHODS: Recruit deaths from 1977 through 2001 were identified and confirmed through redundant sources. Complete demographic, circumstantial, and medical information was sought for each case and recorded on an abstraction form. Mortality rates per 100,000 recruit-years were calculated by using recruit accession data from the Defense Manpower Data Center. RESULTS: There were 276 recruit deaths from 1977 through 2001 and age-specific recruit mortality rates were less than half of same-age U.S. civilian mortality rates. The majority (72%) of recruit deaths were classified as nontraumatic and 70% of these deaths (139 of 199) were related to exercise. Of the exercise-related deaths, 59 (42%) were cardiac deaths, and heat stress was a primary or contributory cause in at least 46 (33%). Infectious agents accounted for only 49 (25%) of the nontraumatic deaths. Nontraumatic death rates increased with age (rate ratio is 2.5 for 25+ v <25 years; p<0.001). The age- and gender-adjusted nontraumatic death rates were 2.6 times higher for African American than non-African American recruits (p<0.001). CONCLUSIONS: Although recruit mortality rates are lower than the same-age U.S. civilian population, preventive measures focused on reducing heat stress during exercise might be effective in decreasing the high proportion of exercise-related death. The availability of 25 years of comprehensive recruit mortality data will permit the ongoing evaluation of cause-of-death trends, effectiveness of preventive measures, and identification of emerging threats during basic military training.

Adolescent↗
PubMed2004

Polymorphism of the Plasmodium falciparum multidrug resistance and chloroquine resistance transporter genes and in vitro susceptibility to aminoquinolines in isolates from the Peruvian Amazon.

In vitro drug sensitivity to chloroquine (CQ), mefloquine (MQ) and quinine was investigated in 60 culture-adapted Plasmodium falciparum isolates from malaria patients in Padrecocha, a village in the Amazonian Department of Loreto, Peru. All isolates showed resistance to CQ, decreased susceptibility to quinine, and sensitivity to MQ. These isolates were examined for mutations in the P. falciparum multidrug resistance 1 (pfmdr1) and chloroquine resistance transporter (pfcrt) genes previously linked to CQ resistance. The mutations N86Y and D1246Y, two of the five mutations commonly observed in the pfmdr1 gene of CQ-resistant clones, were not found. The pfcrt mutation K76T, associated with CQ resistance, was identified in all the isolates tested. Sequence analysis of codons 72-76 in the pfcrt gene showed the haplotypes SVMNT and CVMNT.

Animals↗
PubMed2003

Devices for rapid diagnosis of Malaria: evaluation of prototype assays that detect Plasmodium falciparum histidine-rich protein 2 and a Plasmodium vivax-specific antigen.

The ParaSight F test was developed as a pioneer industry effort in the large-scale, process-controlled production of a device for the rapid diagnosis of malaria. This device performed well in field settings but was limited to the detection of a single malaria species, Plasmodium falciparum. The ParaSight F+V assay advanced upon the ParaSight F test format by incorporating a monoclonal antibody directed against a proprietary Plasmodium vivax-specific antigen, in addition to the antibody directed against P. falciparum histidine-rich protein 2, which was used in the ParaSight F assay. The modified assay was developed to add the capability to detect P. falciparum and P. vivax in a single-test-strip format. The present study evaluated three distinct ParaSight F+V prototypes with samples from symptomatic patients in regions of Thailand and Peru where malaria is endemic. Over a 2-year enrollment period (1998 and 1999), a total of 4,894 patients consented to participation in the study. Compared with the results for duplicate microscopic examinations of Giemsa-stained blood smears as the reference diagnostic standard, each successive prototype showed substantial improvement in performance. The final ParaSight F+V prototype, evaluated in 1999, had an overall sensitivity for detection of asexual P. falciparum parasites of 98%. The sensitivity of the device was 100% for P. falciparum densities of >500 parasites/ micro l, with a sensitivity of 83% for parasite densities of </=500/ micro l. The specificity for the exclusion of P. falciparum was 93%. For P. vivax, the overall sensitivity was 87% for the final 1999 prototype. The sensitivities calculated for different levels of P. vivax parasitemia were 99% for parasite densities of >5,000/ micro l, 92% for parasite densities of 1,001 to 5,000/ micro l, 94% for parasite densities of 501 to 1,000/ micro l, and 55% for parasite densities of 1 to 500/ micro l. The specificity for the exclusion of P. vivax was 87%. The areas under the receiver operating characteristic curves for the diagnostic performance of the assay for the detection of P. falciparum and P. vivax were 0.8907 and 0.8522, respectively. These findings indicate that assays for rapid diagnosis have the potential to enhance diagnostic capabilities in those instances in which skilled microscopy is not readily available.

Animals↗
PubMed2003

Co-infection with malaria and leptospirosis.

Malaria and leptospirosis are both common in the tropics. Simultaneous infections are possible, although not previously reported. We report two cases of malaria from an area of Thailand on the Thailand-Myanmar border with compelling serologic evidence of simultaneous acute leptospirosis. One was a case of infection with Plasmodium falciparum with acute and convalescent microscopic agglutination test (MAT) titers for Leptospira serovar icterohaemorrhagiae of 1:200 and 1:1,600, respectively. The other was a case of infection with P. vivax that seroconverted to a titer of 1:3,200 for Leptospira serovar bataviae. Additionally, there were five probable cases of leptospirosis with patent malaria parasitemia (three P. falciparum and two P. vivax) detected. Management of dual infections is complicated by their similar clinical presentations, and because the confirmatory diagnosis of malaria is readily available as opposed to that of leptospirosis. Treatment focusing on malaria mono-infections instead of dual infections could result in a delay of specific therapy for leptospirosis and possible consequences of serious complications.

Adult↗
PubMed2003

Rapid diagnostic devices for malaria: field evaluation of a new prototype immunochromatographic assay for the detection of Plasmodium falciparum and non-falciparum Plasmodium.

The NOW ICT Malaria P.f./P.v. for Whole Blood (Binax, Inc., Portland, ME) is a new malaria rapid diagnostic device that represents a technical advance over previous assays, such as ICT Malaria P.f./P.v. and ICT Malaria P.f.. We evaluated this device in March 2001 in symptomatic patients at malaria clinics in Maesod, Thailand. Microscopic examination of Giemsa-stained blood smears was the reference standard. In 246 patients, microscopy showed 32 (13.0%) infected with Plasmodium falciparum, 63 (25.6%) with P. vivax, 6 (2.4%) with mixed infections of P. falciparum and P. vivax, 5 (2.0%) with P. malariae, and 140 (56.9%) negative. Sensitivity for P. falciparum was 100% and specificity was 96.2% (200 of 208; 95% confidence interval [CI] = 92-98). For P. vivax, sensitivity was 87.3% (55 of 63; 95% CI = 77-93) and specificity was 97.7% (173 of 177; 95% CI = 95-99), but all the four false-positive results were microscopically positive for P. malariae; thus, specificity for non-falciparum Plasmodium was 100%. These results suggest improved performance over NOW ICT predecessors.

Adult↗
PubMed2002

Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum.

Widespread use of antimalarial agents can profoundly influence the evolution of the human malaria parasite Plasmodium falciparum. Recent selective sweeps for drug-resistant genotypes may have restricted the genetic diversity of this parasite, resembling effects attributed in current debates to a historic population bottleneck. Chloroquine-resistant (CQR) parasites were initially reported about 45 years ago from two foci in southeast Asia and South America, but the number of CQR founder mutations and the impact of chlorquine on parasite genomes worldwide have been difficult to evaluate. Using 342 highly polymorphic microsatellite markers from a genetic map, here we show that the level of genetic diversity varies substantially among different regions of the parasite genome, revealing extensive linkage disequilibrium surrounding the key CQR gene pfcrt and at least four CQR founder events. This disequilibrium and its decay rate in the pfcrt-flanking region are consistent with strong directional selective sweeps occurring over only approximately 20-80 sexual generations, especially a single resistant pfcrt haplotype spreading to very high frequencies throughout most of Asia and Africa. The presence of linkage disequilibrium provides a basis for mapping genes under drug selection in P. falciparum.

Alleles↗
PubMed2002

The prevention of malaria.

Long before the advent of modern chemoprophylaxis drugs, many practitioners successfully prevented the debilitating and fatal outcomes associated with infection by the Plasmodium parasites that cause malaria. Today, with effective insect repellents and several excellent medications available for chemoprophylaxis, there has never been a better array of quality products to prevent mosquito bites and infection and to suppress parasites once in the blood stream; however, there are thousands of imported cases into nonendemic countries and scores of deaths and near-fatal outcomes every year in returning travelers, soldiers, immigrants, and refugees. In this article, the author focuses on practical uses of currently available prevention tools.

Animals↗
PubMed2002

Anemia in parasite- and recombinant protein-immunized aotus monkeys infected with Plasmodium falciparum.

Plasmodium falciparum-induced anemia was characterized in Aotus monkeys repeatedly immunized by infection with P. falciparum (FVO strain) parasites, then cross-challenged with CAMP strain, or in monkeys receiving blood stage challenges as part of malaria vaccine trials. In 4 studies, 25 (30.5%) of 82 monkeys had at least a 50% reduction in hematocrit; mean day of maximum parasitemia was 12.5, whereas the mean day of minimum hematocrit was 18.8 (P < 0.0009). Decreased hematocrit levels were not associated with reticulocytosis until parasite densities decreased significantly from peak levels. Direct antibody tests to detect IgG and C3d on the surface of erythrocytes were negative. Nonantibody/noncomplement-mediated lysis of uninfected erythrocytes seems to be the principal cause of the anemia, and it also seems that bone marrow suppression and lysis of infected erythrocytes contributed to the anemia. Partial immunity-whether induced by repeated immunization with whole parasites or with vaccine-seems important to the development of anemia.

Anemia↗